Research article

Implication of Xenobiotic Metabolizing Enzyme gene (CYP2E1, CYP2C19, CYP2D6, mEH and NAT2) Polymorphisms in Breast Carcinoma

Achraf Khedhaier¹ , Elham Hassen¹ , Noureddine Bouaouina^1,2 , Sallouha Gabbouj¹ , Slim Ben Ahmed³ and Lotfi Chouchane^1,4

¹Laboratoire d'Immuno-Oncologie Moleculaire, Faculté de Médecine de Monastir, Tunisia

²Department of Cancérologie Radiothérapie CHU Farhat Hached, Sousse, Tunisia

³Department of Service de Carcinologie Médicale, CHU Farhat Hached, Sousse, Tunisia

⁴Department of Genetic Medicine, Weill Cornell Medical College in Qatar, Qatar

author email corresponding author email

BMC Cancer 2008, 8:109doi:10.1186/1471-2407-8-109

Published:	18 April 2008

Abstract

Background

Xenobiotic Metabolizing Enzymes (XMEs) contribute to the detoxification of numerous cancer therapy-induced products. This study investigated the susceptibility and prognostic implications of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene polymorphisms in breast carcinoma patients.

Methods

The authors used polymerase chain reaction and restriction enzyme digestion to characterize the variation of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene in a total of 560 unrelated subjects (246 controls and 314 patients).

Results

The mEH (C/C) mutant and the NAT2 slow acetylator genotypes were significantly associated with breast carcinoma risk (p = 0.02; p = 0.01, respectively). For NAT2 the association was more pronounced among postmenopausal patients (p = 0.006). A significant association was found between CYP2D6 (G/G) wild type and breast carcinoma risk only in postmenopausal patients (p = 0.04). Association studies of genetic markers with the rates of breast carcinoma specific overall survival (OVS) and the disease-free survival (DFS) revealed among all breast carcinoma patients no association to DFS but significant differences in OVS only with the mEH gene polymorphisms (p = 0.02). In addition, the mEH wild genotype showed a significant association with decreased OVS in patients with axillary lymph node-negative patients (p = 0.03) and with decreasesd DFS in patients with axillary lymph node-positive patients (p = 0.001). However, the NAT2 intermediate acetylator genotype was associated with decreased DFS in axillary lymph node-negative patients.

Conclusion

The present study may prove that polymorphisms of some XME genes may predict the onset of breast carcinoma as well as survival after treatment.